Development and characterization of [123I]iodotiagabine for in-vivo GABA-transporter imaging

The increased knowledge of molecular changes associated with different neurological disorders calls for the development of novel radioligands. Tiagabine (Gabitril) is an anticonvulsive drug that binds selectively to GABA transporter-1 and thereby inhibits GABA uptake. As radioligands for in-vivo imaging of the GABA transporter are not yet available, we radiolabelled tiagabine and assessed its efficacy for in-vivo imaging of these transporters. Tiagabine was first brominated at its vinylic part, which was then exchanged with I. Next, anaesthetized rats received a bolus injection of [I]iodotiagabine in their tail vein, which was immediately followed by acquisition of planar and high-resolution micro-single-photon emission computed tomography (SPECT) images of the total body with special focus on the brain. Uptake in anatomical regions was assessed by coregistration of micro-SPECT with micro-CT images. Tiagabine labelling with I resulted in 50% yield and 99.7% radiochemical purity. Within 3 h after injection, SPECT demonstrated an increased signal-to-background ratio in the nasal mucosa and/or the Harderian glands but not in the brain. In addition we observed an increased signal-to-background ratio in organs such as the thyroid, heart, liver, kidney and bladder. More than 99% pure I-labelled tiagabine can be obtained and applied in animal micro-SPECT studies. However, this new radioligand is not taken up sufficiently by the brain and therefore cannot be used to successfully detect cerebral GABA transporters.